Subdural Pressure and Brain Condition During Propofol Vs Isoflurane - Nitrous Oxide Anaesthesia in Patients Undergoing Elective Supratentorial Tumour Surgery

Summary Total intravenous anaesthesia has received much importance than inhalational anaesthesia in neuroanaesthetic practice. In an effort to determine whether any important clinical differences occur, studies concerning intracranial pressure (ICP), degreeof dural tension and degree of brain swellingduring intravenousand inhalational based anaesthesia are warranted like the present one. A total of 68 patients were assigned randomly to one of two groups. In Group-I(n=34), anaesthesiawas induced with propofol (1-3mg.kg -1 ) and maintained with propofol (6-10mg.kg -1 .hr -1 ) and fentanyl(2-3mcg.kg -1 .hr -1 ). In GroupII (n=34), anaesthesia was induced with propofol (1-3mg.kg -1 ) but maintained with isoflurane, nitrous oxide and fentanyl (2-3mcg.kg -1 .hr -1 ). Moderate hypocapnia was applied to maintain arterial carbon dioxide around 30mmHg. Mean arterial blood pressure was stabilized with phenylephrine whenever necessary. Subdural intracranial pressure, mean arterial pressure, cerebral perfusion pressure were monitored before and after 10min period of hyperventilation. Furthermore, the tension of dura before and after of hyperventilation and the degree of brain swelling after opening of dura were also estimated by the neurosurgeon. No differences were found between thegroups with regards to demographics, neuroradiologicdiagnosis, posi-tion of head and time of ICP measurement. Before hyperventilation, both ICP and dural tension were significantly lower in Group I compared with Group-II ( P <0.05). But after hyperventilation there was no significant difference of ICP and dural tension in between groups. The degree of brain swelling after opening of dura was similar in both groups. There was a positive correlation between measured ICP and brain swelling score.


Subdural Pressure and Brain Condition During Propofol Vs Isoflurane -Nitrous Oxide Anaesthesia in Patients Undergoing Elective Supratentorial Tumour Surgery
Sankari Santra 1 , Bibhukalyani Das 2

Summary
Total intravenous anaesthesia has received much importance than inhalational anaesthesia in neuroanaesthetic practice. In an effort to determine whether any important clinical differences occur, studies concerning intracranial pressure (ICP), degree of dural tension and degree of brain swelling during intravenous and inhalational based anaesthesia are warranted like the present one.
A total of 68 patients were assigned randomly to one of two groups. In Group-I(n=34), anaesthesia was induced with propofol (1-3mg.kg -1 ) and maintained with propofol (6-10mg.kg -1 .hr -1 ) and fentanyl (2-3mcg.kg -1 .hr -1 ). In Group-II (n=34), anaesthesia was induced with propofol (1-3mg.kg -1 ) but maintained with isoflurane, nitrous oxide and fentanyl (2-3mcg.kg -1 .hr -1 ). Moderate hypocapnia was applied to maintain arterial carbon dioxide around 30mmHg. Mean arterial blood pressure was stabilized with phenylephrine whenever necessary. Subdural intracranial pressure, mean arterial pressure, cerebral perfusion pressure were monitored before and after 10min period of hyperventilation. Furthermore, the tension of dura before and after of hyperventilation and the degree of brain swelling after opening of dura were also estimated by the neurosurgeon. Majorgoals ofneurosurgicalanaesthesiaare maintenance of haemodynamic stability, sufficient cerebral perfusion pressure, relaxed brain to facilitate neurosurgical resection and avoidance of agents or procedures that increase intracranialpressure (ICP).

Introduction
There has been longstandingcontroversy regarding use of inhalationalor intravenous anaesthetic agent for intracranialprocedure. Totalintravenous anaesthesia has always received much importance to avoid ce-rebral vasodilating effect of nitrous oxide (N 2 O) and volatile agents. But so far no study comparing intravenous with volatile based anaesthesia has been able to demonstrate major outcome difference 1,2 . However most of these studies examined aheterogenous patient population and ICP measured bydifferent techniques.
Severalexperimental and clinical studies of cerebral haemodynamics including cerebral blood flow (CBF), cerebralmetabolism for oxygen (CMRO 2 ), ICP have been conducted during isoflurane 3,4 , propofol [5][6][7] anaesthesia. Only few comparative studies of ICP are available. In one prospective trial, where three anaesthetic techniques (isoflurane-N 2 O, N 2 O-fentanyl, propofol-fentanyl) were used for elective supratentorialcraniotomy, epidural ICP was measured through burr hole. Though ICPdid notdiffer significantly, more patients with isoflurane-N 2 O group had ICP greater than 24mmHgas compared to othertwo groups 1 .Other studies monitoringlumbar cerebrospinal fluid (CSF) pressure demonstrated conflictingresults, eitherno difference of ICP during propofol versus thiopentoneisoflurane anaesthesia 2 or significantly lower ICP during propofol compared to isoflurane 8 .
During craniotomy one of the most critical point is opening of dura where a high ICP may cause some degree of brain swelling 9 . SubduralICP measurement after removal of bone flap is a regional estimate of ICP which is influenced by presence of space occupying lesion (SOL) 10 and gravity 11 . In one study, the level of subdural ICP and intraventricular pressure correlated wellwith thedural tensionand thedegree ofbrain swellingafter openingof dura, estimatedby neurosurgeons, blinded to the levelof ICP 12 . In a recent trial, subdural ICP and incidence of brain swelling after opening of dura were significantly lower during propofol anaesthesia when comparedto isoflurane and sevoflurane. 13 The primary goal of present study was to detect any difference in subduralICPoccured duringpropofol versus isoflurane-nitrous oxide anaesthesia along with theeffectofhyperventilation in patientsundergoingelective craniotomy for supratentorial tumour. Degree of duraltension and brain swelling after openingof the dura were also studied as secondary objectives.

Methods
The study was undertaken at Bangur Institute of Neuroscience and Psychiatry after approvalofthe protocol by localethical committee. It was a prospective randomized trial.Verbal andwritten consent was taken from all patients.
Sixty eight patients of age 18to 65years, of either sex, American Society ofAnesthesiologists physical status I and II, Glasgow Coma Scale (GCS) of 15 undergoing electivecraniotomy forsupratentorial tumour resection were randomly allocated in one of the two groups. Group I-Propofol ( n= 34) , Group II-Isoflurane-nitrous oxide (n=34).
Patients diagnosedas havingsupratentorialtumour with midline shift of less than10mm (revealed by cerebralcomputed tomographyor magnetic resonance imaging) wereincluded in this study. Medically controlled hypertension or diabetes mellitus were also included.
Patients were excluded if they suffered from ischaemic heart disease, congestive heart failure, renal or hepatic dysfuntion, or severe chronic respiratory disease.

Anaesthesia and monitoring:
The patients were premedicated with 150mg oral ranitidine one hour prior to anaesthesia. Preoperative corticosteroid, anticonvulsant, antihypertensive were administeredas usual.Monitoring beforeinduction consisted of automated noninvasive blood pressure, continuous electrocardiogram and pulse oximetry. After induction of anaesthesia, a radial artery catheter was inserted with zero pressure adjustment at mid-axillary line forcontinuous bloodpressure monitoringand blood sampling. Urine output and rectal temperature were continuously monitored throughout the procedure. Inspired and end-tidaloxygen, carbon dioxide, nitrous oxide and isoflurane were measured. Lungs were mechanically ventilated to maintain an arterial blood carbon-dioxide tension between 30-40mmHgand inspiratory peak pressure less than 20cm of H 2 O. Train offour was used to monitor muscular relaxation which was achieved by a continuous infusion of atracurium. The anaesthetic procedures were as follows.

Subdural Intracranial Pressure measurement, Estimation of Dural tension and Brain swelling:
After removalof boneflap, a22G/0.8mm venflon cannula was placed under dura and connected to a pressure transducer system via a polyethylene catheter. Zero level of ICP was adjusted with the transducer kept at the level of orbitomeatalline. After 1minute of stabilization meanvalue of subdural pressure was used as anestimate of ICP. After initial measurement of ICP, pulmonary ventilation was increased by 30% (increasingrate and tidalvolume) for 10min. SubduralICP was again measured at 11 th min after first measurement. Cerebralperfusion pressure (CPP) was calculated as the difference between mean arterialpressure (MAP) and ICP.
Estimation of dural tension was made in a scale of four, using tactile evaluation by neurosurgeon. Neurosurgeons wereblinded to anaesthetic technique. The tension was categorized as follows: (1) very slack (2) normal (3) increased tension (4) pronounced increased tension. The degree of brain swelling was evaluated by theneurosurgeon afteropeningof the dura. Degree of swelling was estimated and categorized as follows (1) no swelling, excellent operating condition (2) minimum swelling (3) moderate swelling and (4) pronounced swelling of the brain

Statistical analysis
Based on a previous study of ICP, given a minimaldetectable significant difference of 3.5mmHg, expected SD 5.0mmHg, power of 0.80, and a statistical significance levelof P<0.05, the totalsample size (number of patients) was calculated to be 68. Data within groups were tested for normaldistribution. Two sample t-test was applied for parametric data (ICP, MAP, CPP). Chi-square test was used for analysis of demographic data, localization, size and histopathologic diagnosis of the tumours, preoperative drug administration between the groups. Difference in dural tension and brain swelling were tested by chi-square test in 2x4 tables. For correlation, Pearson product moment correlation and linear regression were performed. Data were expressed as mean ±SD. P<0.05 was considered statistically significant.

Results
A total of 68 patients were enrolled in the study with equal number of 34 patients in each group. Demographic data are shown in Table-1. There were no significant differences between the groups in terms of age, sex, weight andASA grading. Table-2. There were no difference in neurological diagnosis ( site, type and size of tumour) and number of patients taking antihypertensive or anticonvulsant. The number of patients requiringblood pressure support, differed significantly between groups and total dose of vasopressor used also was significantly higher in propofol group than isoflurane-nitrous oxide group.

Clinicaldata includingtime interval between induction and ICP measurement andvasopressor administration are shown in
After removal of bone flap subdural ICP, MAP were measured and CPP was derived and are summarized in Table-3. Before hyperventilation, there was no   significant difference of MAP and CPP in between groups but subdural ICP was significantly lower in propofol group than isoflurane-nitrous oxide group. After hyperventilation ICP decreased significantly in isoflurane-nitrous oxide group. Difference in PaCO 2 (before and after hyperventilation) was greater in propofol group but reduction in ICP after hyperventilation was significantly smaller as compared to isoflurane-nitrous-oxide group.
Theduraltensionbefore andafter hyperventilation as estimated by neurosurgeon, are shown in Table 4.

Discussion
Different anaestheticagents have different effects on cerebral haemodynamics. For example, propofol decreases CBF, ICP and may decrease cerebral perfusion pressure via its effects on blood pressure. 14 Isoflurane appears to produce moderate increase in CBF and pronounced decrease in cerebral metabolism.An increase in ICPcaused by it may be mild and can be prevented by hypocapnia 15 .Severalgroupshave shown that it can increase ICP or decrease cerebral perfusion pressure in neurosurgicalpatients. [16][17][18] Nitrous oxide is also a potent vasodilatorand can increase CBF and ICP when given either aloneor incombination with a volatile agent. [19][20][21] But this increase can be attenuated by prior administration of thiopentone and hypocapnia 22 . Opioids are assumed to have no important effects as long as ventilation is controlled. Recently sufentanil, alfentaniland fentanylhave been reported to increase ICP and CBF 23,24 although this has not been observed uniformly 25 andallthree drugs havebeen used successfully in neuroanaesthesia.
Despite these concerns, there is no clinical evidence that one particular anaestheticmanagement regimen is superior to other. The few available comparative trials suggest no important difference between propofol versus isoflurane, nitrous oxide versus no nitrous oxide. 2,26,27 In the current study, we found that subdural ICP and the degree of dural tension were significantly lower during propofol anaesthesia as compared toisoflurane-nitrous oxide anaesthesia but after hyperventilation there was no statisticaldifference between twogroups. Both before and after hyperventilation, a significantly lower CPP was found in propofol group. Asignificant differencewas foundregarding phenylephrine administrationwith regard to number of patients and totaldose requirement.
In comparative studies of lumbar CSF pressure in patientswithout spaceoccupying lesion subjected to desflurane, isoflurane, sevoflurane and propofol anaesthesia,a higherCSF pressure was foundduring volatile anaesthesia compared with propofol anaesthesia 8,16 .  Before hyperventilation,dural tension was significantly higher in isoflurane-nitrous oxide group but after hyperventilation there was nosignificant difference in between groups. Degree of brain swelling after opening of dura, asshown in Table-5, wassimilar inboth groups.
There was a positive correlation between measured ICP and brain swelling score as wellas neurological data (tumour size and midline shift) and brain swelling score.
In another study of lumbar CSF pressure in neurosurgical patients subjected to either propofol-fentanyl or thiopental-isoflurane-fentanylanaesthesia, no significant difference of lumbar CSF pressurewas recorded 2 .
Subdural pressure is more accurate as a regional estimate 10,11 compared with lumbar CSF pressure measurement because tumour or cerebraledema localized close to craniotomy increases subduralpressure more than lumbar CSF pressure. In addition, obliteration of CSF pathway caused by tumour makes lumbar CSF pressure less reliable. No significant difference in epidural ICP was recorded in another comparative study of propofoland isoflurane-nitrous oxide anaesthetized patients. 1 In principle, their findings corroborate with those of current study. Methodologic differencesin ICP monitoring might explainthe comparativelylower ICP values in our study.
In this study, brain swellingafter openingof dura was similarin both groups. Neurosurgeonswere blinded to anaesthetic technique. In another study no difference was mentioned regarding brain swelling between isoflurane-N 2 O and propofol/fentanyl group 1 . However, asignificant correlation was found between brain swelling score and ICP.
In clinical studies, cerebral autoregulation is preserved with propofolbut is impaired during1.5 MAC isoflurane. 28,29 Assuch, a higher CPPduringisofluranenitrous oxide anaesthesiashould elicit a decrease in ICP. The question of whether cerebralautoregulation influences ICP is further complicated by the fact that cerebral autoregulationis impaired or abolished in patients with cerebral tumours. 30 In this study, isoflurane administration was restricted to well defined and low MAC level (1 MAC) and maintenance doses of propofol and fentanyl were well defined. Accepted mean arterial blood pressure reduction was 20%, otherwise vasopressor was administered.
In this study, the decrease in ICPafter hyperventilation averaged 1.5mmHg in the propofol group but 3mmHg in isoflurane-N 2 O group. The significantly greater decrease in ICP during isoflurane-nitrous oxide anaesthesia may be due to better carbon dioxide responsiveness. This is inagreement with other clinical studies indicating a preserved carbon dioxide reactivity during anaesthesia with isoflurane 4,31 but decreased carbon dioxide reactivity during anaesthesia with propofol. 32,33 .
Itis temptingto conclude that oneanaesthetic regimen is better than other. Each anaesthetic has advantages and disadvantages. As noted, isoflurane and nitrous oxide are vasodilators and both can increase ICP. In contrast, totalintravenous anaesthesia consisting of propofoland fentanyl (without nitrous oxide) should reduce CBF and ICP. But combination of low dose isoflurane with nitrous oxideand fentanylmight cause an intermediate increase in CBF and ICP because concentration of either drug can be decreased than concentration ofany agent when usingalone to provide an anaesthetic plane requiredfor surgicalresection. None of the anaesthetic was associated with any intra operative difficulties.
We designed the current trial in such a manner that the subject population was as uniform as possible and we restricted the trial to patients with known supratentorialtumourswith midlineshift less than 10mm. Although supratentorial surgery in patients with large tumour might revealdifferences, in this study, any significant difference in subduralICP and brain condition for surgery after hyperventilation was not revealed in both groups. Limitation of the study were firstly inability to estimate carbon dioxide reactivity, inability to defineabsolute endpoints ofanaesthesia in both groups in absence of anaesthetic depth monitor. Thecurrent studyindicates thatduringcraniotomy for supratentorial cerebral tumours, subdural ICP is lower in patients anaesthetized with propofol than isoflurane-nitrous oxide.After hyper ventilation, there were no significant difference of ICP and dural tension. Degree ofbrain swellingafter openingof durawas similar in both groups. CPP was higher , may be due to better preservation of carbon dioxide responsiveness in isoflurane-nitrous oxide group as compared with propofol group. These results support the view that despite their cerebrovascular effects, institution of hyperventilation makes bothanaesthetic regimens equally acceptable for intracranialtumour surgery.